The purpose of this study is to clarify the role of family genetic and family environmental influences in the development of substance use, problems and dependence, associated psychopathology, and psychosocial functioning. We propose to interview by telephone: adolescent and young adult offspring of fathers who are twins concordant for, or discordant for history of DSM-3R Drug Dependence (DD), with or without Alcohol Dependence (AD) (" PSuD"), or who are concordant unaffected (N=527 twin pairs); their twin fathers; and their biological mothers. Offspring will be interviewed 2 years later as well. Because our design controls for genetic influences on offspring by including twin-fathers concordant for PSuD, it permits identification of environmental variables important in the development of offspring substance problems, associated psychopathology, and behavioral and other problems. We are able to identify such twins and their families from data collected in the NIDA-funded Harvard Drug Study in which a structured psychiatric diagnostic interview administered to over 8000 twins (3372 complete pairs) in the Vietnam-era Twin Registry (VETR) elicited detailed information about PSuD and other psychiatric disorders. A special aspect is our planned capitalization on assessments and data being collected already in 2 studies of children of AD twins (COAT) from the VETR twin panel, which not only will expedite our fieldwork, but will permit comparison of offspring of PSuD) twin-fathers (this study) to offspring of AD-only fathers (COAT). We have 5 aims: 1) to determine whether and to what extent offspring of PSuD twins compared to offspring of non-PSuD twins and offspring of AD-only twins differ in retard to illicit and licit drug use, abuse and dependence, other associated psychopathology, and functioning; 2) to determine to what extent there are differences in transitions in substance involvement, other psychopathology, and functioning between offspring of {PSuD twins and their unaffected cotwins, after controlling for genetic liability; 3) to control for maternal effects (e.g., assortative mating) on offspring outcomes; 4) to study modifiers in the development of offspring outcomes; 5) to analyze data jointly with those from offspring of: ADVETR AD twins. Our study will move beyond estimation of the magnitude of genetic and environmental influences on substance development to a fuller understanding of genetic and environmental influences that explain how family history of PSuD predisposes offspring to adverse outcomes, including substance problems, associated psychopathology, and poor psychosocial functioning.